Research accomplishments 1. We have defined an environmental signaling axis that regulates the stability of a regulatory subunit of the human Mi-2/NuRD complex. This signaling pathway may play a role in determination of phenotypic properties of malignant cells. 2. We have identified a role for the Mi-2/NuRD complex in the process of chromosome duplication and have made progress in understanding how this complex plays a role in this process. Our data suggest the existence of a previously undescribed checkpoint monitoring chromatin quality during the process of chromosomal duplication. 3. We have begun exploration of chromatin modifications and their relationship to gene expression in primary cells from mice. 4. We have utilized genomic scale analysis of DNA methylation to identify epigenetic alterations in B lymphocytes that occur druring immune activation. We have tied these epigenetic alterations to transcription factor and DNA methyltransferase function. 5. We have made significant progress in understanding the genomic distribution of NuRD complex in breast cancer cells and how this enzyme contributes to the biological program of breast cancer. 6. We have begun analysis of genome modification in an exposure model of cancer.